Glial cells derived from pluripotent stem cells as a suitable tool for modeling Alzheimer’s disease

Abstract

AbstractBackgroundAlzheimer's disease (AD) is characterized by presenting a complex pathology, not fully resolved yet. This fact, together with the lack of reliable models, has impeded the development of effective therapies. Recently, several studies have shown that functional glial cell defects have a key role in the pathology of AD. However, this glial dysfunction, currently, cannot be correctly modeled using the available animal models, so we hypothesized that cells derived from Alzheimer's patients can serve as a better platform for studying the disease. In this sense, human pluripotent stem cells (hPSC) allow the generation of different types of neural cells, which can be used for disease modeling, identification of new targets and drugs development.MethodWe have a collection of hiPSCs derived from patients with sporadic forms of AD. We have differentiated these cells towards neural lineage to obtain neurons and astrocytes. For the generation of oligodendrocytes (OLs), we have developed a fast and robust protocol to generate mature OLs in just 22 days.ResultWe have generated neural precursors from all the lines tested. In the case of OLs, the cells generated resemble primary OLs and can myelinate neurons in vivo and in vitro using a screening compatible platform. This platform is being transferred for the generation of the other glial cells.ConclusionThis methodology can be used to elucidate the pathogenic pathways associated with neurodegeneration and to identify new therapeutic targets susceptible to modulation, contributing to the development of new effective drugs against AD. Acknowledgments: J.A.G.L has been supported by a contract of doctor reincorporation plan from the I Plan Propio of the University of Malaga (Spain) and by CIBERNED. The work was supported by Instituto de Salud Carlos III (ISCiii) of Spain, co‐financed by FEDER funds from European Union (grant PI18/01557 to A.G., grant P18/1556 to JV), by Junta de Andalucia co‐financed by FEDER funds grant UMA18‐FEDERJA‐211 (to AG), by Consejeria de Salud of Junta de Andalucia (grant PI‐0276‐2018 to J.A.G.L.) and by CIBERNED.